Alzheimer's disease is reportedly an organic brain disease with primary lesions within the brain and its etiology remains for the most part unraveled. However, the current knowledge suggests that Alzheimer's disease is a disease entity characterized by organic brain damages at least secondary to some preceding causative event, and the therapeutic modality so far proposed comprises curing the underlying disease inducing this organic disturbance of the brain or removing or otherwise disposing of the pathogenic factor or factors directly involved in the expression of such organic disturbance.
The underlying disease in Alzheimer's disease is multi-pronged, including cerebrovascular disorders (e.g. cerebral apoplexy associated with cerebral hemorrhage and infarction, hypertension, angitis, vascular anomaly, etc.), degenerative diseases (e.g. Pick's disease, Parkinson's disease, epilepsy, hydrocephalus, etc.), endocrine diseases (e.g. myxedema, Addison's disease, hypothyroidism, hypoglycemia, vitamin deficiencies, etc.), metabolic diseases (e.g. uremia, hepatic disorder, anoxia, etc.), intoxications (e.g. carbon monoxide poisoning, manganese poisoning, alcoholism, barbiturism, Korsakoff's syndrome, etc.), infectious diseases (e.g. chronic encephalitis), tumorigenic diseases (e.g. remote effects of cancer), and traumatic diseases (e.g. head injury).
Referring to the etiologic factors directly involved in the onset of Alzheimer's disease, the gene abnormality theory (Alzheimer gene, Down's syndrome gene, etc.), abnormal protein deposition theory amyloid protein (senile plaque) theory, neurofibrillary tangle theory, etc.!, and aluminum accumulation theory have been advanced.
The onset and progression of Alzheimer's disease is considered to arise from a complicated interaction of the above-mentioned underlying disease inducing Alzheimer's disease and the etiologic factor or factors directly inducing the expression of Alzheimer's disease.
JP-A-3 81218 (U.S. Pat. No. 5,059,627) reports that substituted 1,4-benzoquinone derivatives including idebenone and the corresponding hydroquinone derivatives have nerve growth factor secretion-inducing activity and are effective in the treatment of Alzheimer's disease.
JP-A-7 61923 (EP-A-629400) reports that high doses of idebenone are clinically effective in the therapy of senile dementia of Alzheimer type.
The Lancet, 340, 671(1992) reports that a combination therapy using coenzyme Q.sub.10, an iron preparation, and vitamin B.sub.6 is effective in the therapy and inhibition of progression of familial Alzheimer's disease.
JP-A-1 221316 discloses a nootropic composition comprising idebenone in combination with vinpocetine.
However, no report is available on a therapeutic or prophylactic medication for Alzheimer's disease that ever employs idebenone in combination with other medicinal substances.
For the method of treating and preventing Alzheimer's disease involving a multiplicity of etiologic factors as mentioned above, therapeutic drugs for the underlying diseases have been used independently for symptomatic relief only with limited success. Moreover, the only symptomatic remedy for Alzheimer's disease that has been available so far is tacrine (1,2,3,4-tetrahydro-9-acridinamine hydrochloride) and donepezil (2,3-dihydro-5,6-dimethoxy-2-1-(phenylmethyl)-4-piperidinyl!methyl!-1H-i nden-1-one hydrochloride) which, however, have the drawback of hepatotoxicity and/or other cholinergic side effects.